The bioavailability of an administered substance is that fraction of the dose that reaches the general circulation unchanged. The general circulation is defined experimentally by the sampling site, usually a blood vessel in the peripheral circulation. Fig.1 is a schematic representation of drug movement after oral ingestion. As the drug passes down the gastrointestinal tract, part of the dose may not be available for absorption because of chemical degradation, physical inactivation through binding or complexation, microbial biotransformation, etc. Of that which is absorbed at x , some may be metabolized in transit through the gut wall. Unchanged drug that reaches the hepatic portal vein p may be extracted by the liver by way of biotransformation or biliary excretion. Finally, further elimination may occur between the hepatic vein h and the site of measurement, say a peripheral vein j or a peripheral artery a .